Remdesivir-d4

Remdesivir-d₄ is intended for use as an internal standard for the quantification of remdesivir by GC- or LC-MS. Remdesivir is a prodrug form of the antiviral nucleoside analog GS-441524 .^1,2 Upon entry into cells, remdesivir is metabolized into a nucleoside monophosphate form, which is further metabolized to an active nucleotide triphosphate that induces RNA chain termination and inhibits viral polymerases.³ Remdesivir reduces viral titers in primary human airway epithelial (HAE) cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV) or severe acute respiratory syndrome CoV (SARS-CoV; EC₅₀s = 0.074 and 0.069 µM, respectively). It reduces infectious virus production in SARS-CoV-2-infected HAE cells (EC₅₀ = 10 nM).⁴ In vivo, remdesivir (25 and 50 mg/kg) reduces lung viral titers and prevents weight loss in a mouse model of SARS-CoV infection.² Remdesivir (25 mg/kg) also reduces lung viral titers and lung hemorrhage and improves pulmonary function in mice infected with a chimeric SARS-CoV encoding the SARS-CoV-2 RNA-dependent RNA polymerase (RdRP).⁴ Formulations containing remdesivir have been used in the treatment of COVID-19.

1.Agostini, M.L., Andres, E.L., Sims, A.C., et al.Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonucleasemBio9(2)e00221-00218(2018) 2.Sheahan, T.P., Sims, A.C., Graham, R.L., et al.Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronavirusesSci. Transl. Med.9(396)eaal3653(2017) 3.Eastman, R.T., Roth, J.S., Brimacombe, K.R., et al.Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19ACS Cent. Sci.6(5)672-683(2020) 4.Pruijssers, A.J., George, A.S., SchÄfer, A., et al.Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in miceCell Rep.32(3)107940(2020)